Protein detection is important for a number of fields, ranging from proteomics to medicine. The gold standard of protein detection is the ELISA assay, which uses antibodies to recognize antigens present in picomolar concentrations. However, the constraints on antibody stability and preparation (particularly when creating many different antibodies) severely limit their use. Overall, the field of detection still lacks a general method for accessing robust receptors for any given antigen. Therefore, we aim to replace traditional antibodies with "chemical antibodies" that are made from organic small molecules. Chemical antibodies will form by lateral self-assembly of gold nanoparticle-bound small molecules in response to an added antigen. Pre-organization of the small molecules onto a surface will decrease the entropic penalties associated with self-assembly, facilitating the "evolution" of one high-affinity and selective receptor. After assembly of the chemical antibody, the positions of the small molecules will be fixed by surface polymerization, creating a stable receptor that can be recycled for multiple uses. Antigen binding will be detected, possibly down to zeptomolar concentrations, by measuring changes in the light scattering properties of the gold nanoparticles. As a result of these studies, a new procedure will be available for rapidly generating chemical antibodies with affinities and selectivities similar to traditional antibodies (ideally), but without the stability and availability issues of the natural biopolymers. These chemical antibodies should be available in quantity, and will be used to create disease-specific detection devices that are less expensive, more stable, and easier to implement than those used currently. As a starting point, chemical antibodies that recognize prostate-specific antigen will be pursued during this funding period. In the long run, these chemical antibodies also may be useful for therapeutic applications. Relevance to Public Health: The technology outlined in this proposal could have immediate applications for the early detection of cancer. The chemical antibodies presented here may be more stable, more versatile, and ultimately more sensitive than the antibody-based detection methods used today. [unreadable] [unreadable] [unreadable]